Since many patients with congenital malformations of the heart are now living into their child-bearing years thanks to diagnostic and surgical advances, the question of inheritance of such abnormalities has become of great concern. The incidence of congenital heart defects (CHD) in the offspring of parents who have cardiac anomalites has been considered to be 3-5%. A recent prospective study by this investigator, however, has revealed an incidence of some 16% in 372 progeny of 233 affected women. No study has identified the recurrence risk in the offspring of fathers with CHD. The 400-500 children of approximately 300 affected fathers are to be examined to determine this incidence. These fathers will be selected by a random technique from the same clinic population as was used for the maternal study, which in turn will be updated. Comparable family history involving all first degree relatives, and medical pedigree of both the maternal and paternal side of each child, will be obtained and submitted to careful analysis in conjunction with clinical and population geneticists. The incidence of CHD in the offspring of affected men will be compared with those of affected women. It is anticipated that empiric risk factors may be calculated, the mode of inheritance clarified in certain instances, and some genetic mechanisms concerning congenital malformations of the heart become apparent. The sex differences between various malformations will also be addressed. Any information thus derived from these two comparable studies would yield results of considerable predictive value for genetic counseling.